Low noncarbonic buffer power amplifies acute respiratory acid-base disorders in patients with sepsis: an in vitro study

Abstract

Rationale: Septic patients have typically reduced concentrations of hemoglobin and albumin, the major components of non-carbonic buffer power(β). This could expose patients to high pH variations during acid-base disorders. Objectives: To compare, in-vitro, non-carbonic β of septic patients with that of healthy volunteers, and evaluate its distinct components. Methods: Whole blood and isolated plasma of 18 septic patients and 18 controls were equilibrated with different CO2 mixtures. Blood gases, pH and electrolytes were measured. Non-carbonic β and non-carbonic β due to variations in Strong Ion Difference (βSID) were calculated for whole blood. Non-carbonic β and non-carbonic β normalized for albumin concentrations (βNORM) were calculated for isolated plasma. Representative values at pH=7.40 were compared. Albumin proteoforms were evaluated via two-dimensional electrophoresis. Measurements and Main Results: Hemoglobin and albumin concentrations were significantly lower in septic patients. Septic patients had lower non-carbonic β both of whole blood (22.0±1.9 vs. 31.6±2.1 mmol/L, p<0.01) and plasma (0.5±1.0 vs. 3.7±0.8 mmol/L, p<0.01). Non-carbonic βSID was lower in patients (16.8±1.9 vs. 24.4±1.9 mmol/L, p<0.01) and strongly correlated with hemoglobin concentration (r=0.94, p<0.01). Non-carbonic βNORM was lower in patients (0.01 [-0.01 - 0.04] vs. 0.08 [0.06 - 0.09] mmol/g, p<0.01). Septic patients and controls showed different amounts of albumin proteoforms. Conclusions: Septic patients are exposed to higher pH variations for any given change in CO2 due to lower concentrations of non-carbonic buffers and, possibly, an altered buffering function of albumin. In both septic patients and healthy controls, electrolyte shifts are the major buffering mechanism during respiratory acid-base disorders.

Combining the Physical–Chemical Approach with Standard Base Excess to Understand the Compensation of Respiratory Acid–Base Derangements: An Individual Participant Meta-analysis Approach to Data from Multiple Canine and Human Experiments

“…In this context, the strong ion difference change represents the metabolic adaptation and is mirrored by standard base excess. Of note, a similar relationship between standard base excess and acute or chronic Paco 2 variations was described in humans by Schlichtig et al 35 Last, in line with previous studies, 4,36 our data from acute experiments underline the dependency of "plasma" strong ion difference on Paco 2 . While one might argue that this observation discredits the physical-chemical approach, we think that a reallocation of independent variable status from "plasma" to "extracellular" strong ion difference (i.e., strong ion difference of whole blood and interstitial fluid) reconciles the model.…”

“…29,30 Last, a quantitatively less important cause of both sodium and chloride acute shifts is their direct pH-dependent release from plasma proteins. 4,31 During chronic hypercapnia, the kidneys are responsible for the observed chloride variation, mainly due to the excretion of ammonium chloride. 32 While the renal response to an acid-base disorder is extremely powerful and rapidly established, 33 it requires up to 1 week to fully compensate for respiratory acid-base alterations.…”

Intravenous fluid therapy in patients with severe acute pancreatitis admitted to the intensive care unit: a narrative review

“…Normal plasma SID ranges between 33–40 mEq/L, according to the used definition. A reduction in SID, shifts the system toward acidosis while an increase in SID toward alkalosis [ 92 ]. The SID of infused crystalloids (after metabolism of the organic anions) might, therefore, significantly alter plasma SID and, therefore, affect pH [ 85 , 86 ].…”

Understanding base excess (BE): merits and pitfalls

“…As direct titration is obviously impossible in a clinical scenario, nomograms and formulae were developed to estimate BE. The most common equation, which is still in use, is the following: where 24.8 and 7.40 are the reference, ideal HCO 3 − (mmol/L) and pH values, and β is the buffer power (mmol/L) of non-carbonic weak acids [7,8], which can either be a constant value (16.2 mmol/L) or computed as a function of hemoglobin concentration (assuming a constant protein concentration of 70 g/L) [9,10]. The β value, multiplied by the variation in pH, provides an estimate of the change in weak negative charges due to noncarbonic buffers.…”